Nocistatin and nociceptin given centrally induce opioid-mediated gastric mucosal protection.
Nociceptin (N/OFQ) and nocistatin (NST) are two endogenous neuropeptides derived from the same precursor protein, preproN/OFQ. The aim of the present work was to study the effect of NST on the ethanol-induced mucosal damage compared with that of N/OFQ following intracerebroventricular (i.c.v.) administration in the rat and to analyze the mechanism of the gastroprotective action. It was found that both NST and N/OFQ reduced the mucosal lesions in the same dose range (0.2-1 nmol i.c.v.), but in higher doses (2-5 nmol i.c.v.) the gastroprotective effect of both peptides was highly diminished. The gastroprotective effect of N/OFQ (1 nmol), but not that of NST (1 nmol), was reduced by the selective nociceptin receptor antagonist J-113397 (69 nmol i.c.v.). Similarly, decrease of the gastroprotective effect was observed after the combination of NST (1 nmol) with N/OFQ (0.6 or 1 nmol). However, addition of the gastroprotective effects was observed, when lower dose (0.2 nmol) of NST was given prior to N/OFQ (0.6 nmol). The gastroprotective effect of both N/OFQ and NST was antagonized by naloxone (27 nmol), beta-funaltrexamine (20 nmol), naltrindole (5 nmol) and norbinaltorphimine (14 nmol), the mu-, delta- and kappa-opioid receptor antagonists, respectively, given i.c.v. The mucosal protection was significantly decreased after bilateral cervical vagotomy. The present findings suggest that NST similar to N/OFQ, may also induce gastric mucosal protective action initiated centrally in a vagal-dependent mechanism. Opioid component is likely to be involved in the gastroprotective effect of both NST and N/OFQ.
Zádori
Zoltán S
ZS
Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Semmelweis University, Nagyvárad tér 4., 1089 Budapest, Hungary.
Shujaa
Nashwan
N
Köles
László
L
Király
Kornél P
KP
Tekes
Kornélia
K
Gyires
Klára
K
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D007276:Injections, Intraventricular / Q000379:methods; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy; D014628:Vagotomy; D000097629:Nociceptin
D001562:Benzimidazoles; D000431:Ethanol; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D010880:Piperidines; D011957:Receptors, Opioid; D000097629:Nociceptin; C402921:J 113397; C111148:nocistatin